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Objectives: To examine the relationship between ambient temperature and DTR and pregnancy outcomes in vitro fertilization/intracytoplasmic monosperm injection and embryo transfer (IVF/ICSI-ET) women., Methods: The study included 5264 women who were treated with IVF/ICSI-ET at two centers in Hubei province from 2017 to 2022. The daily mean, daily maximum, and daily minimum temperatures at the subjects' home addresses were extracted, and DTR values were calculated based on latter two. The associations between ambient temperature and DTR with clinical pregnancy and live birth rates were assessed using multivariate logistic regression models adjusted for covariates. Subgroup analyses were also conducted to explore potential modifiers., Result: High/low temperatures as well as a larger DTR had a significant effect on pregnancy outcomes in fresh cycles, but not in FET cycles. Specifically, hot weather exposure to high temperatures was associated with reduced clinical pregnancy rates: Period 4 (embryo transfer to serum HCG testing) (aOR = 0.873, 95%CI: 0.763-0.999). Ambient temperature in cold weather was positively associated with live birth rate: Period 2 (Gn initiation to oocyte retrieval) (aOR = 1.082, 95% CI: 1.01-1.170), Period 3 (oocyte retrieval to embryo transfer) (aOR = 1.111, 95% CI: 1.019-1.212), Period 4 (aOR = 1.134, 95% CI: 1.028-1.252), and Period 7 (85 days prior to oocyte retrieval to serum hCG testing) (aOR = 1.105, 95% CI: 1.007-1.212). For DTR, exposure to larger DTR (Q3) at Period 2, Period 3, and Period 6 (Gn initiation to embryo transfer) reduces clinical pregnancy and live birth rates compared with Q1. Subgroup analyses revealed susceptibility profiles across age groups and residential address populations in different sensitivity windows., Conclusion: Our study shows that exposure to hot and cold weather and higher DTR reduces clinical pregnancy rates and live birth rates in women undergoing fresh embryo transfer, but has no significant effect on FET cycles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dibutyl phthalate is a chemical commonly used as a plasticizer in the production of daily necessaries, such as cosmetics and toys. Although several toxic effects of dibutyl phthalate have been confirmed, those related to pregnancy are unknown. Trophoblasts are critical for fetal and placental development, and trophoblast damage may cause preeclampsia. This study aimed to confirm the toxic effect of dibutyl phthalate on trophoblasts. We used the human trophoblast cell line HTR-8/SVneo and human choriocarcinoma JEG-3 cells as a placental trophoblast model to investigate the toxic effects of dibutyl phthalate. Both cell lines were treated with dibutyl phthalate (0-20 μg/mL) to verify the mechanisms regulating trophoblast function. Dibutyl phthalate treatment significantly reduced trophoblast viability, reduced invasion ability, and induced mitochondrial depolarization. Ultimately, dibutyl phthalate regulated the PI3K and MAPK signaling pathways and the expression of autophagy-related proteins ATG5, LC3B, and SQSTM1/p62. We concluded that dibutyl phthalate induced autophagy and effectively weakened trophoblast function. Additionally, we conducted experiments to assess the potential effects of monobutyl phthalate, a metabolite of dibutyl phthalate, on cellular mobility, penetration, and autophagy induction. Our results demonstrated that monobutyl phthalate impaired these functions and weakened the trophoblast barrier, after dibutyl phthalate metabolized. Thus, exposure to dibutyl phthalate and its metabolite monobutyl phthalate can damage trophoblast function, highlighting their potential as hazardous substances that impair trophoblast barrier integrity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Propanil, an anilide herbicide, has frequently been detected in surface waters in Europe and the United States, largely due to its use in paddy cultivation areas. Particularly in specific regions like Sri Lanka, propanil is considered a potential cause of certain diseases and toxicities due to its high environmental runoff; however, there has been little research on its developmental toxicity. In the present study, we confirmed the developmental toxicity of propanil in zebrafish embryos exposed to 0, 2, 5, and 6 mg/L based on the LC 50 value. Propanil exposure in embryos induced morphological changes, including decreased body length and eye size, and increased the heart and yolk sac edema. It increased the number of apoptotic cells in the brains and eyes of zebrafish larvae by 214 % and 184 %, respectively. Propanil-treated embryos exhibited altered mitochondrial metabolism, reducing basal respiration by 28 %, maximal respiration by 24 %, and ATP production by 38 %. These alterations induced organ defects in transgenic zebrafish models (cmlc2:DsRed, flk1:EGFP, olig2:DsRed, lfabp:DsRed;elastase:EGFP, and insulin:EGFP). It induced cardiovascular toxicity, as confirmed by the reduced atrial area, cerebrovascular intensity, and intersegmental vessels. Additionally, propanil decreased the fluorescence intensity of neurons, liver, and pancreas. Collectively, this study indicates that propanil causes early developmental toxicity through apoptosis and mitochondrial dysfunction. It presents a new perspective on how mitochondrial dysfunction, previously unreported in toxicity studies of other anilide herbicides, may affect developmental toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The gut microbiome is critical for the pathophysiology of depression, and inflammation is one of the factors contributing to depression. Fzd6 has been implicated in depression. This study aimed to elucidate the effects of the Fzd6 mutation on gut microbiota structure and the possible regulatory mechanisms involved in depression-associated neuroinflammation., Methods: Wild-type (Fzd6 WT ) and Fzd6 mutant (Fzd6 Q152E ) male mice were treated with lipopolysaccharide (LPS) for 7 days. Behavioral experiments were used to detect the behavioral changes of mice in each group, and the composition of intestinal flora and systemic inflammation levels of mice were further detected., Results: In LPS mice, the Fzd6 mutation enhanced depression-like behavior symptoms, increased the release of pro-inflammatory cytokines, decreased the release of anti-inflammatory cytokines, and caused intestinal flora disturbance. Subsequently, 16SrRNA sequencing revealed significant changes in the relative abundance of the inflammation-associated bacterial groups Ruminococcaceae and Lachnospiraceae in Fzd6 Q152E mice. In mice with depression, the levels of G protein-coupled receptors, GPR41 and GPR43, and glucagon-like peptide-1 (GLP-1) in the small intestine were down-regulated, and the expression of GLP-1 receptor (GLP-1R), peroxisome proliferators activated receptors gamma (PPAR-γ), and nuclear factor kappa-B inhibitor alpha (IκBα) in the hippocampus was also down-regulated, while the expression of nuclear factor kappa-B p65 (NF-κB p65) was up-regulated., Limitations: The size of the spleen was not studied in this model, and the Fzd6 mutation itself does not cause systemic inflammation such as IL-6., Conclusion: These results demonstrate that mutations in Fzd6 regulate the composition of the gut flora, which contributes to depression-associated inflammation., Competing Interests: Declaration of competing interest The authors declare that there are no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

The dynamic regulation of chromatin accessibility is one of the prominent characteristics of eukaryotic genome. The inaccessible regions are mainly located in heterochromatin, which is multilevel compressed and access restricted. The remaining accessible loci are generally located in the euchromatin, which have less nucleosome occupancy and higher regulatory activity. The opening of chromatin is the most important prerequisite for DNA transcription, replication, and damage repair, which is regulated by genetic, epigenetic, environmental, and other factors, playing a vital role in multiple biological progresses. Currently, based on the susceptibility difference of occupied or free DNA to enzymatic cleavage, solubility, methylation, and transposition, there are many methods to detect chromatin accessibility both in bulk and single-cell level. Through combining with high-throughput sequencing, the genome-wide chromatin accessibility landscape of many tissues and cells types also have been constructed. The chromatin accessibility feature is distinct in different tissues and biological states. Research on the regulation network of chromatin accessibility is crucial for uncovering the secret of various biological processes. In this review, we comprehensively introduced the major functions and mechanisms of chromatin accessibility variation in different physiological and pathological processes, meanwhile, the targeted therapies based on chromatin dynamics regulation are also summarized., Competing Interests: Competing interests: The authors declare no competing interest. Consent for publication: All authors have read the manuscript and consent to publication, (© 2024. The Author(s).)

Altered tissue mechanics is vital for cancer development and malignancy, whether targeting the mechanical microenvironment could retard the initiation and progression of tumor is less explored. In this study, an orthotopic hepatocellular carcinoma (HCC) rat model was constructed to reproduce the mechanical and pathophysiological microenvironment of HCC development. LpMSN@CLG, a liver-targeted (L) and pH-sensitive (p) mesoporous silica nanoparticle (MSN) encapsulated with collagenase type-I (CLG), and DOX-LpMSN@CLG, on the basis of LpMSN@CLG, encapsulated with CLG and doxorubicin (DOX), were prepared to reduce matrix stiffness by degrading collagen in liver and HCC tumor. LpMSN@CLG, and DOX-LpMSN@CLG were respectively injected (i.v.) into rats at the stage of fibrosis and HCC, resulting in decreased collagen content in liver and HCC tissue, as well as reduced matrix stiffness. In addition, LpMSN@CLG treatment at the fibrosis stage retarded HCC initiation, and DOX-LpMSN@CLG treatment inhibited the growth of HCC tumor when compared with that of the rats treated by DOX alone, suggesting that reducing matrix stiffness in HCC tumor can improve the therapeutic efficacy of DOX. Taken together, our study demonstrated that mechanical intervention of tissue stiffness by CLG-loaded nanoparticles could retard the initiation and progression of HCC, suggesting the promising of mechanical intervention of hepatocellular carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Oral flora and inflammatory factors play a crucial role in oral cancer, but the relationship between them and oral cancer has not been clearly established., Methods: Oral flora served as exposure factor, oral cancer as outcome factor, and inflammatory factors as mediating factor. Mendelian randomization (MR) analysis was used to analyze the relationship between oral flora and oral cancer, and the potential mediating effect of inflammatory factors was explored through mediation analysis., Results: 29 kinds of oral flora in tongue coating and 22 kinds of oral flora in saliva were associated with increased risk of oral cancer. 18 species of oral flora in tongue coating and 25 species in saliva were associated with a reduced risk of oral cancer. Interleukin-8 (IL8) played a mediating role in the relationship between oral flora and oral cancer, and it was associated with an increased risk of oral cancer. Granulicatella, Streptococcus mitis, Saccharimonadaceae and Haemophilus in oral flora caused oral cancer indirectly through IL8. IL8 expression increased in oral cancer, which has good diagnostic value. IL8-related genes in oral cancer are closely associated with immune cell infiltration. What's more, IL8 has potential medicinal properties., Conclusion: Oral flora of tongue coating and saliva is closely related to oral cancer, and IL8 plays a mediating role in the causal relationship between oral flora and oral cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Accurate estimation of atmospheric chemical concentrations from multiple observations is crucial for assessing the health effects of air pollution. However, existing methods are limited by imbalanced samples from observations. Here, we introduce a novel deep-learning model-measurement fusion method (DeepMMF) constrained by physical laws inferred from a chemical transport model (CTM) to estimate NO 2 concentrations over the Continental United States (CONUS). By pretraining with spatiotemporally complete CTM simulations, fine-tuning with satellite and ground measurements, and employing a novel optimization strategy for selecting proper prior emission, DeepMMF delivers improved NO 2 estimates, showing greater consistency and daily variation alignment with observations (with NMB reduced from -0.3 to -0.1 compared to original CTM simulations). More importantly, DeepMMF effectively addressed the sample imbalance issue that causes overestimation (by over 100%) of downwind or rural concentrations in other methods. It achieves a higher R 2 of 0.98 and a lower RMSE of 1.45 ppb compared to surface NO 2 observations, overperforming other approaches, which show R 2 values of 0.4-0.7 and RMSEs of 3-6 ppb. The method also offers a synergistic advantage by adjusting corresponding emissions, in agreement with changes (-10% to -20%) reported in the NEI between 2019 and 2020. Our results demonstrate the great potential of DeepMMF in data fusion to better support air pollution exposure estimation and forecasting.

Background Context: Due to the rarity and heterogeneity, paraspinal soft-tissue sarcomas represent a unique and challenging clinical entity for musculoskeletal oncologist. Reports on the treatment of paraspinal soft-tissue sarcoma are limited and the best treatment modality for this rare sarcoma type has not yet been well defined., Purpose: To introduce a modified classification of paraspinal sarcoma, review the outcome of patients treating in our center and determine the effective treatment for paraspinal soft-tissue sarcoma., Study Design/setting: Retrospective review of prospectively collected data., Patient Sample: The study included patients with paraspinal soft-tissue sarcomas in our center., Outcome Measures: Clinical outcomes, complications and survival., Methods: Twenty-five patients with paraspinal soft-tissue sarcomas treating at our center from April 2017 to December 2023 were retrieved from the hospital database. The treatment of these patients included surgery, chemotherapy, radiation, targeted therapy and immunological therapy according to respective tumor type. Patient demographics, tumor characteristics, treatment history, clinical outcomes and survival were collected from electronical medical records., Results: According to the modified classification of paraspinal sarcoma, Type 1 tumors were diagnosed in 15 cases, Type 2 in 4, Type 3 in 5 and Type 4 in 1. All the patients received surgery. No patients in the study received intralesional resection, wide or marginal margins were achieved. Eleven patients received post-operative radiotherapy. The median follow-up duration in this study was 27 months (range 8-67 months). Three patients suffered from wound infection post-operatively and were successfully treated by debridement and antibiotics. Three patients had muscular weakness after surgery and gained improved muscular strength with rehabilitation. There was no implant failure complication. Three recurrence cases were recorded. Four patients died of brain or lung metastasis. Five patients survived with the disease and the remaining 16 patients were alive with disease free., Conclusions: Correct pathological diagnosis before treatment is vital, and the modified classification can guide the surgical strategy for paraspinal soft-tissue sarcoma. Paraspinal soft-tissue sarcoma is best treated by comprehensive treatment approach with surgery as the main method, which can yield good outcomes., (Copyright © 2024. Published by Elsevier Inc.)

When making risky choices in social contexts, humans typically combine social information with individual preferences about the options at stake. It remains unknown how such decisions are made when these preferences are inaccessible or disrupted, as might be the case for individuals confronting novel options or experiencing cognitive impairment. Thus, we examined participants with lesions in insular or dorsal anterior cingulate cortex, key regions implicated in risky decision-making, as they played a gambling task where choices were made both alone and after observing others' choices. Participants in both lesion groups showed disrupted use of standard utility-based computations about risky options. For socially situated decisions, these participants showed increased conformity with the choices of others, independent from social utility-based computations. These findings suggest that in social contexts, following others' choices may be a heuristic for decision-making when utility-based risk processing is disrupted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Orloff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, an analytical model was developed to predict the sound absorption performance of fibrous absorbers fabricated using an extrusion-based three-dimensional (3D) printing method. The proposed model employs geometric design parameters, including the average fiber diameter and the horizontal and vertical fiber separations, to calculate the porosity, static airflow resistivity, tortuosity, and viscous and thermal characteristic lengths. These transport parameters are then used within the Johnson-Champoux-Allard semiempirical formulation to predict the normal incidence sound absorption coefficient. The analytical model was validated by comparing the calculated properties with those obtained using the finite element-based hybrid numerical modeling method and those estimated through direct and indirect experimental measurements. Finally, by using the validated analytical model, the effect of each geometrical design parameter on the sound absorption performance of the 3D-printed fibrous absorbers was investigated, revealing that the absorption behavior is primarily controlled by the static airflow resistivity and showing that high absorption peaks and a broadband absorption profile can be achieved by adjusting the three geometrical parameters. This study highlights the potential of 3D printing to fabricate fibrous sound absorbers with tailored acoustic properties, offering a promising solution for advanced noise control materials., (© 2024 Acoustical Society of America.)

Transcatheter aortic valve replacement (TAVR) procedure was planned for a 68-year-old female patient diagnosed with severe aortic stenosis by transthoracic echocardiography. The first valve unexpectedly dislodged during catheter tip withdrawal after full deployment. A second valve deployment became necessary, posing challenges due to the difficulty of passing the second valve delivery system through the first valve frame. The snare technique is typically used in cases where there are difficulties in delivering the transcatheter heart valve system across the native aortic valve during the TAVR procedure. We described a novel bailout technique to capture the delivery system in the main access using a snare catheter from the secondary access, while retaining the stiff wire in the left ventricle. This technique could be particularly applicable in scenarios where recrossing is challenging and risky., (© 2024 Wiley Periodicals LLC.)

The interaction of Mesomycoplasma (Mycoplasma) ovipneumoniae (M. ovipneumoniae) with host cells is a pivotal step in the infection process, underlining the necessity to develop vaccines and therapeutic approaches targeting the pathogen's key invasion mechanisms. The bacterium's capacity for adherence, invasion, and subsequent evasion of the host immune response underpins its pathogenicity, rendering adherence genes feasible vaccine targets. This study focuses on pyruvate dehydrogenase complex component E3 (PdhD), a membrane-anchored surface protein implicated in these pathogenic processes. Bioinformatics analysis reveals the conservation of PdhD sequence within M. ovipneumoniae. Membrane protein extraction, immunoblotting and ELISA assay have confirmed the presence of PdhD on the M. ovipneumoniae surface and cytoplasm, suggesting its multifunctionality. Our research employed antibody inhibition assays to characterize the bacterial adhesion suppression by anti-PdhD antibodies, complemented by bactericidal complement assays, supporting its candidacy as a putative vaccine target. The ELISA binding assay substantiated that PdhD binded to plasminogen (Plg) in a dose-dependent manner. Notably, PdhD is also involved in biofilm formation. The inhibitory effect of anti-PdhD sera on biofilm formation is congruent with novel therapeutic strategies targeting related mycoplasmas. This study reports the characterization of the first virulence-associated protein PdhD of M. ovipneumoniae and suggests its potential as a vaccine target to combat M. ovipneumoniae infection., Competing Interests: Declaration of Competing Interest The authors declare no competing interests for the present work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Elevated levels of butyrylcholinesterase (BuChE) have the potential to be predictive in the timely detection and diagnosis of Alzheimer's disease (AD). By inhibiting of BuChE activity can raise acetylcholine levels and intervene AD processes. Therefore, BuChE as an important factor in treatment AD has been given more and more attention in clinical studies. Given the facts above, in this study, for precise monitoring of BuChE level changes and screening for possible butyrylcholinesterase inhibitor (BuChEI) for AD diagnosis and therapy, a near-infrared (NIR) fluorescence probe (NFP-BuChE) was created. The probe exhibits excellent sensitivity and selectivity for BuChE. NFP-BuChE has been successfully applied to the detection of endogenous BuChE levels in live cells, and we successfully constructed a screening system for BuChEI on cells and a novel natural efficient BuChEI (matrine) was discovered and identified, which significantly reduced BuChE activity and thus alleviated AD symptoms. Most importantly, for the first time, we measured the changes of BuChE levels in zebrafish (0-4 days) after fertilization, various organs of zebrafish, and AD zebrafish modeled by different concentrations of AlCl 3 by NFP-BuChE, and at the same time, we also validated the inhibitory effect of matrine on BuChE by NFP-BuChE in zebrafish. In addition, NFP-BuChE has also been successfully used to measure the changes of BuChE levels in the brains of AD mice. These findings imply that NFP-BuChE is a potentially useful molecular tool for screening possible natural BuChEI quickly and for monitoring changes in BuChE activity, and it is expected that more value will be explored in mice. In addition, matrine and its derivatives are promising options for future Alzheimer's disease treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study aimed to investigate the impact of Urolithin A (UA) on muscle endurance, muscle strength, inflammatory levels, oxidative stress, and protein metabolism status in resistance-trained male athletes., Method: An 8-week randomized, double-blind, placebo-controlled study was conducted with twenty resistance-trained male athletes. Participants were supplemented with 1 g of UA daily. Muscle strength and muscle endurance measures were assessed, and fasting venous blood samples and morning urine samples were collected to evaluate their oxidative stress levels, inflammatory markers, and protein metabolism status., Results: There were no significant differences observed in terms of dietary energy intake and composition between the two assessments conducted within a 24-hour period. After 8 weeks of UA supplementation, compared to baseline measurements, the UA group exhibited increases in 1RM bench press and squat, although these changes were not statistically significant (Δ = 3.00 ± 0.17 kg, p  = 0.051, Δ = 1.35 ± 2.73 kg, p  = 0.499). However, significant improvements were noted in Maximum Voluntary Isometric Contraction (MVIC) and repetitions to failure (RTF) performance (Δ = 36.10 ± 0.62 NM, p  = 0.000; Δ = 2.00 ± 0.56, p  = 0.001). When compared to the placebo group, the UA supplementation for 8 weeks led to an increase in 1RM bench press and squat, although statistical significance was not reached (Δ = 3.50 ± 0.79 kg, p  = 0.462; Δ = 2.55 ± 1.36 kg, p  = 0.710). Furthermore, the group receiving UA supplementation, compared to the placebo group, showed significant improvements in MVIC and RTF (Δ = 43.50 ± 0.77 NM, p  = 0.048; Δ = 2.00 ± 1.22, p  = 0.011), indicating that the UA group exhibited superior performance enhancements in these metrics compared to the placebo group. After 8 weeks of UA supplementation, the UA group showed a significant decrease in 3-methylhistidine (3-MH) compared to baseline measurement (Δ=-2.38 ± 1.96 μmol/L, p  = 0.049). Additionally, the UA group exhibited a significant increase in C-reactive protein (CRP) compared to baseline (Δ = 0.71 ± 0.21 mg/L, p  = 0.001). However, there was no significant changes observed in Interleukin-6 (IL-6) (Δ=-1.00 ± 1.01 pg/mL, p  = 0.076), or superoxide dismutase (SOD) (Δ=-0.004 ± 0.72 U/mL, p  = 0.996) compared to baseline in the UA group. When compared to the placebo group, there was no significant difference observed in 3-MH in the UA group (Δ=-3.20 ± 0.31 μmol/L, p  = 0.36). In terms of inflammation markers, the UA group exhibited a significant decrease in CRP (Δ=-0.79 ± 0.38 mg/L, p  = 0.032) compared to the placebo group, whereas there was a decrease in IL-6 without statistical significance (Δ=-1.75 ± 0.45 pg/mL, p  = 0.215). Furthermore, the UA group showed a significant decrease in SOD compared to the placebo group (Δ=-4.32 ± 0.90 U/mL, p  = 0.041)., Conclusions: After 8 weeks of UA supplementation at 1 g/day, resistance-trained male athletes showed improvements in muscle strength and endurance. Additionally, UA supplementation was also associated with reduced oxidative stress levels and a decrease in inflammation response levels.

A novel instantaneous tiltmeter with dynamic and static monitoring functions is reported that is based on liquid metal dynamic wetting behavior in a bio-fabricated anisotropic microchannel. The proposed system achieves instantaneous tiltmeter functionality, offering a broad detection range (-90°-90°) with high precision (0.05°), a rapid reaction time (0.11 s), and enhanced durability. Moreover, a seamless integration has enabled water wave detection, language programming, and human limb monitoring. Especially, the integration of tiltmeter and a 3D motion platform results in a surface structure scanning system capable of effectively performing large area (>200 cm 2 ) and height difference scanning functions. This innovative approach holds great potential for transformative changes in the fields of advanced manufacturing, flexible robotics, and the flexible sensing, further facilitating widespread adoption., (© 2024 Wiley‐VCH GmbH.)

Fiber elongation rate is an essential characteristic of cotton fiber in the textile industry, yet it has been largely overlooked in genetic studies. Gibberellins (GAs) and auxin (IAA) are recognized for their role in directing numerous developmental processes in plants by influencing cell differentiation and elongation. However, the degree to which GA-IAA interaction governs cellular elongation in cotton fiber cells remains to be fully understood. In this study, we identified a causal gene, Gibberellic Acid-Stimulated in Arabidopsis 24 (GhGASA24), that appears to be responsible for fiber elongation rate via regulating fiber cell wall thickness. Subsequent experiments revealed that GhGASA24 influences cell wall formation by promoting the expression of GhCesA8 and GhCesA10. Our findings suggest that Auxin Response Factor 2 (GhARF2) regulates fiber elongation rate by directly binding to the AuxRE elements in GhGASA24 promoter. In addition, we identified Growth Regulation Factor 4 (GhGRF4) as a transcription factor that interacts with GhARF2 to form a heterodimer complex, which also transcriptionally activates GhGASA24. Intriguingly, GhGRF4 regulates GhARF2 expression by directly binding to its promoter, thereby acting as a cascade regulator to enhance the transcriptional levels of GhGASA24. We propose that the GhGRF4/GhARF2-GhGASA24-GhCesAs module may contribute to fiber cell wall thickness by modulating cellulose biosynthesis, and provide a theoretical basis for improvement of fiber quality., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Magnetic particle imaging (MPI) has emerged as a novel technology utilizing superparamagnetic nanoparticles as tracers, essential for disease diagnosis and treatment guidance in preclinical animal models. Unlike other modalities, MPI provides high sensitivity, deep tissue penetration, and no signal attenuation. However, existing MPI tracers suffer from "always-on" signals, which complicate organ-specific imaging and hinder accuracy. To overcome these challenges, we have developed a responsive MPI tracer using pH-responsive PdFe alloy particles coated with a gatekeeper polymer. This tracer exhibits pH-sensitive Fe release and modulation of the MPI signal, enabling selective imaging with a higher signal-to-noise ratio and intratumoral pH quantification. Notably, this responsive tracer facilitates subtraction-enhanced MPI imaging, effectively eliminating interference from liver uptake and expanding the scope of abdominal imaging. Additionally, the tracer employs a dual-function mechanism for adaptive cancer therapy, combining pH-switchable enzyme-like catalysis with dual-key co-activation of ROS generation, and Pd skeleton that scavenges free radicals to minimize Fe-related toxicity. This advancement promises to significantly expand MPI's applicability in diagnostics and therapeutic monitoring, marking a leap forward in imaging technology., (© 2024 Wiley‐VCH GmbH.)

The bacteria-algae synergistic wastewater treatment process not only efficiently eliminates nutrients and absorbs heavy metals, but also utilizes photosynthesis to convert light energy into chemical energy, generating valuable bioresource. The study systematically explores the formation, algal species, and regulatory strategies of the bacterial-algal symbiosis system. It provides a detailed analysis of various interaction mechanisms, with a particular focus on nutrient exchange, signal transduction, and gene transfer. Additionally, the efficacy of the system in removing nitrogen, phosphorus, and heavy metals, as well as its role in CO 2 reduction and bioresource recycling, is thoroughly elaborated. Potential future research of bacteria-algae cell factory producing bioenergy production, feed or fertilizers are summarized. This paper clearly presents effective strategies for efficiently removing pollutants, reducing carbon emissions, and promoting resource recycling in the field of wastewater treatment. It also provides recommendations for further research on utilizing microbial-algal symbiotic systems to remove novel pollutants from wastewater and extract value-added products from the resulting biomass., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Resmethrin, a type I pyrethroid insecticide, is frequently used globally in residential and farmland areas to control pests. Owing to the repeated administration of resmethrin, and particularly because of its lipophilic nature, residues have been detected in various environments, crops, and livestock. Previous studies have shown the adverse effects of resmethrin, including neurotoxicity and hepatotoxicity. However, the toxic effects of resmethrin on the female reproductive system have rarely been investigated. In the present study, we used two cell types, porcine trophectoderm (pTr) and porcine uterine luminal epithelial (pLE) cells, to examine the toxic effects of resmethrin on implantation and its mechanisms. Our study showed that resmethrin exposure induced apoptosis and inhibited cell cycle progression, thereby reducing the viability of both cell types. In addition, calcium homeostasis was disrupted following resmethrin treatment, and disrupted calcium homeostasis impaired the mitochondrial membrane potential and mitochondrial respiration. In addition to mitochondrial dysfunction, GRP75 and ER stress-related proteins were upregulated. Furthermore, the AKT and MAPK cascades were altered, and reactive oxygen species production and inflammation occurred after resmethrin treatment. Ultimately, through various mechanisms, resmethrin decreased the migratory abilities, and it could diminish the crosstalk between the two cell lines and lower the probability of successful implantation. Overall, we demonstrated that resmethrin interfered with the implantation process by triggering various toxic mechanisms. This study presents, for the first time, evidence regarding the mechanisms through which resmethrin exerts toxic effects on the female reproductive system, thereby raising awareness regarding the potential implications of its widespread use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Immune-related biomarkers are linked to the outcomes of cancer immunotherapy. This study evaluates the baseline and longitudinal association between the lung immune prognostic index (LIPI) and immune checkpoint inhibitor outcomes in previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) patients., Methods: Data from 153 R/M NPC patients (median age = 49.00 years old) enrolled in a multicenter, single-arm, phase 2 study (NCT03848286) were analyzed. Pretreatment LIPI was classified into good and intermediate/poor (inter/poor) groups. Longitudinal LIPI variations were categorized into "Stable good", "Trend to increase", "Trend to decrease", and "Stable inter/poor". Primary and secondary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR)., Results: Pretreatment LIPI was significantly associated with OS (inter/poor vs. good: HR = 2.54, 95 % CI: 1.60-4.04, P < 0.001), PFS [inter/poor vs. good: hazard ratio (HR) = 2.18, 95 % CI: 1.47-3.23, P < 0.001], and DCR [inter/poor vs. good: odd ratio (OR) = 0.26, 95 % CI: 0.12-0.58, P < 0.001)]. Patients with persistently inter/poor LIPI status showed worse OS (HR = 3.25, 95 % CI: 1.84-5.74, P < 0.001), PFS (HR = 2.96, 95 % CI: 1.85-4.74, P < 0.001), and ORR (OR = 0.21, 95 % CI: 0.08-0.56, P < 0.001) compared to the persistently good subgroup., Conclusion: Pretreatment LIPI and its longitudinal variations may serve as potential biomarkers for predicting immune checkpoint inhibitor outcomes in R/M NPC patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Junyou Ge, Yan Qing, and Youneng Wei reports a relationship with Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to determine the likelihood of hyperglycemia postpartum in women with gestational diabetes mellitus (GDM) and to identify the predictors., Methods: The retrospective cohort study involved 1 527 GDM patients who delivered at Peking University First Hospital from 1 January 2021, to 31 December 2021. According to the blood glucose level of postpartum oral glucose tolerance test (OGTT), women were divided into a normal glucose tolerance (NGT) group and a hyperglycemia group, and their characteristics and risk factors of hyperglycemia were compared., Results: The prevalence of hyperglycemia was 33.9% (184/543) at 6-12 weeks postpartum. Compared with the NGT group, the fasting plasma glucose (FPG) of hyperglycemia group increased significantly during pregnancy and postpartum, the OGTT 1h postprandial glucose (PG) and 2hPG increased in the second trimester of pregnancy, the triglyceride (TG) increased in the first trimester of pregnancy and postpartum, the triglyceride glucose (TyG) index increased in the first trimester of pregnancy and postpartum, and the total cholesterol (TCHO) and low density lipoprotein cholesterol (LDL-C) decreased in the second trimester ( p  < 0.05). Fasting plasma glucose (FPG) in the first trimester [odds ratio (OR) = 3.583, p  < 0.001], OGTT 2hPG in the second trimester (OR = 1.604, p  < 0.001), the TyG index in the first trimester (OR = 1.863, p  = 0.045) and FPG in third trimester (OR = 1.985, p  = 0.024) were independent risk factors for postpartum hyperglycemia., Conclusions: Approximately one-third of women with GDM have hyperglycemia 6-12 weeks after delivery. FPG and the TyG index in the first trimester, OGTT 2hPG in the second trimester and FPG in third trimester are risk factors for postpartum hyperglycemia.

A large amount of sludge is inevitably produced during sewage treatment. Ultrasonication (US) as anaerobic digestion (AD) pretreatment was implemented on different sludges and its effects on batch and semi-continuous AD performance were investigated. US was effective in sludge SCOD increase, size decrease, and CH 4 production in the subsequent AD, and these effects were enhanced with an elevated specific energy input. As indicated by semi-continuous AD experiments, the mean daily CH 4 production of US-pretreated A 2 O-, A 2 O-MBR-, and AO-AO-sludge were 176.9, 119.8, and 141.7 NmL/g-VS added , which were 35.1%, 32.1% and 78.2% higher than methane production of their respective raw sludge. The US of A 2 O-sludge achieved preferable US effects and CH 4 production due to its high organic content and weak sludge structure stability. In response to US-pretreated sludge, a more diverse microbial community was observed in AD. The US-AD system showed negative net energy; however, it exhibited other positive effects, e.g., lower required sludge retention time and less residual total solids for disposal. US is a feasible option prior to AD to improve anaerobic bioconversion and CH 4 yield although further studies are necessary to advance it in practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Disorders of glucose and lipid metabolism are an important cause of type 2 diabetes mellitus (T2DM). Identifying the molecular mechanism of metabolic disorders is key to the treatment of T2DM. The study was to investigate the effect of circRNA PIP5K1A (circPIP5K1A) on glucose and lipid metabolism and inflammation in T2DM rats. A T2DM rat model was established, and then the T2DM rats were injected with lentiviral vectors that interfere with circPIP5K1A, miR-552-3p, or ENO1 expression. Fasting blood glucose (FBG) and fasting insulin (FINS) levels of rats were detected by an automatic analyzer and insulin detection kit, and HOMA-IR was calculated. Lipid metabolism was assessed by measuring serum levels of TG, TC, LDL-C, leptin, and resistin. Serum levels of inflammatory factors (TNF-α and IL-6) were detected by ELISA. The pathological conditions of pancreatic tissue were observed by HE staining. circPIP5K1A, miR-552-3p and ENO1 levels were recorded. The experimental results showed that circPIP5K1A and ENO1 were up-regulated, and miR-552-3p was down-regulated in T2DM rats. Down-regulating circPIP5K1A or up-regulating miR-552-3p reduced blood glucose and lipid levels, inhibited inflammation, and improved pancreatic histopathological changes in T2DM rats. In addition, up-regulating ENO1 rescued the ameliorating effects of down-regulated circPIP5K1A on T2DM rats. In general, downregulating circPIP5K1A improves insulin resistance and lipid metabolism disorders and inhibits inflammation by targeting miR-552-3p to mediate ENO1 expression., Competing Interests: Declarations Conflict of Interests Authors declared no conflict of interest. Ethical Statement All animal experiments were complied with the ARRIVE guidelines and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The experiments were approved by the Institutional Animal Care and Use Committee of Changshu Hospital Affiliated to Soochow University., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The efficacy and safety of new-generation devices (NGDs) for severe aortic regurgitation (AR) have mostly been based on single-arm studies with limited sample sizes. Our goal was to summarize the current evidence on NGDs and compare the safety and efficacy of 'off-label' and 'on-label' devices in NGDs. We searched MEDLINE, Embase, Cochrane Library, and Scopus for articles on transcatheter aortic valve replacement in patients with AR. A total of 31 studies that included 1851 patients were identified through April 2023. Among these, 1067 (57.6%) patients received treatment with 'on-label' devices (JenaValve and J-Valve). For NGDs, the total device success rate at 30 days was 94.5% (on-label: 97.8%, off-label: 89.9%; P < 0.001), the all-cause mortality was 4.2% (on-label: 2.6%, off-label: 5.1%; P = 0.006), permanent pacemaker implantation (PPI) was 8.8% (on-label: 6.9%, off-label: 18.4%; P < 0.001), and the rate of greater-than-mild paravalvular leak (PVL) was 1.2% (on-label: 0.9%, off-label: 3.8%; P = 0.003). On-label devices showed significantly better safety and efficacy in terms of the success rate, PPI, greater-than-mild PVL, and 30 day mortality than off-label devices., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Lipid oxidation in air-fried seafood poses a risk to human health. However, the effect of a prooxidant environment on lipid oxidation in seafood at different air frying (AF) temperatures remains unknown. An integrated machine learning (ML) - guided REIMS and lipidomics method was applied to explore lipid profiles, lipid oxidation, and lipid metabolic pathways of salmons under different AF temperatures (140, 160, 180, and 200 °C). A significant difference in the lipidomic fingerprinting of air-dried salmon at different temperatures was shown by the main ML methods (neural networks, support vector machines, ensemble learning, and naïve bayes). In total, 773 differential expression metabolites (DEMs) were identified, including glycerophospholipids (GPs), glycerides (GLs), and sphingolipids. A total of 34 DEMs with p values <0.05 and variable importance of projection values >1.0 were analyzed, belonging to linoleic acid metabolism, GL metabolism, and GP metabolism pathways. Correlation network analysis revealed that some characteristic DEMs (phosphatidylcholine, lyso-phosphatidylcholine, triglycerides, fatty acids, and phosphatidylethanolamine) were highly correlated with lipid oxidation. In addition, variations of volatile compounds, color values, texture characteristics, and thiobarbituric acid-reactive substance values were analyzed to corroborate the oxidation characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To explore the influence of extracellular vesicles secreted by dural cells (Dura-EVs) on osteoblasts. Our methodology involves assessing the effects of these EVs at concentrations of 50ug/ml, 100ug/ml, and 200ug/ml on osteoblasts proliferation, differentiation, migration, osteogenesis, and inhibition of apoptosis. We also treated a cranial defect model with injections of these Dura-EVs and monitored the healing rate of cranial defects. Tissue sections were analyzed using Hematoxylin and Eosin (H & E), Masson's trichrome, and immunofluorescence (IF) staining. Our results suggest that Dura-EVs can enhance osteoblasts proliferation, migration, differentiation, and osteogenesis in a dose-dependent manner in vitro. In vivo, Dura-EVs may promote the repair of skull defects. Dura-EVs have an important influence on osteoblasts, our findings shed light on a novel aspect of the dura mater's contribution to cranial osteogenesis., Competing Interests: Declarations Conflict of interest The authors declare that there have no conflict of interest to disclose. Ethical Approval The privacy rights of animal subjects were observed. Consent to Participate Not applicable. Consent to Publish Not applicable., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We introduce PICFormer, a novel framework for Pluralistic Image Completion using a transFormer based architecture, that achieves both high quality and diversity at a much faster inference speed. Our key contribution is to introduce a code-shared codebook learning using a restrictive CNN on small and non-overlapping receptive fields (RFs) for the local visible token representation. This results in a compact yet expressive discrete representation, facilitating efficient modeling of global visible context relations by the transformer. Unlike the prevailing autoregressive approaches, we proposed to sample all tokens simultaneously, leading to more than 100× faster inference speed. To enhance appearance consistency between visible and generated regions, we further propose a novel attention-aware layer (AAL), designed to better exploit distantly related high-frequency features. Through extensive experiments, we demonstrate that the PICFormer efficiently learns semantically-rich discrete codes, resulting in significantly improved image quality. Moreover, our diverse image completion framework surpasses State-of-the-Art methods on multiple image completion datasets.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined., Methods: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses., Results: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs . 46.6%, p  <  0. 001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p  < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality ( p  = 0.004), need for renal replacement therapy ( p =  0.011), and developing stage-3 AKI (p =  0.040) according to the adjusted models., Conclusions: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.

Tick-borne encephalitis virus (TBEV) represents a pivotal tick-transmitted flavivirus responsible for severe neurological consequences in Europe and Asia. The emergence of TBEV genetic mutations and vaccine-breakthrough infections, along with the absence of effective vaccines and specific drugs for other tick-borne flaviviruses associated with severe encephalitis or hemorrhagic fever, underscores the urgent need for progress in understanding the pathogenesis and intervention strategies for TBEV and related flaviviruses. Here we elucidate cellular alterations in the proteome, phosphoproteome, and acetylproteome upon TBEV infection. Our findings reveal a substantial impact of TBEV infection on the innate immune response, ribosomal biogenesis, autophagy, and DNA damage response (DDR). Mechanically, the non-structural protein NS5 of TBEV impedes DNA damage repair by interacting with SIRT1 to suppress the deacetylation of KAP1 and Ku70. Additionally, the precursor membrane protein prM induces autophagy via associating with AKT1 while constrains autolysosome formation through binding to VPS11. Inhibitors targeting DDR, as well as specific kinases, exhibit potent antiviral activity, suggesting the dysregulated pathways and kinases as potential targets for antiviral intervention. These results from our study contribute to elucidating the pathogenesis and offers insights for developing effective antiviral drugs against TBEV and other tick-borne flaviviruses., Competing Interests: Competing interests: The authors declare no conflicts of interest., (© 2024. The Author(s).)

Alterations in microbiotas and endogenous enzymes have been implicated in meat deterioration. However, the factors that mediate the interactions between meat quality and microbiome profile were inadequately investigated. In this study, we collected pork samples throughout the refrigeration period and employed metaproteomics to characterize both the pork and microbial proteins. Our findings demonstrated that pork proteins associated with the catabolic process are upregulated during storage compared to the initial stage. Pseudomonas, Clostridium, Goodfellowiella, and Gonapodya contribute to the spoilage process. Notably, we observed an elevated abundance of microbial proteins related to glycolytic enzymes in refrigerated pork, identifying numerous proteins linked to biogenic amine production, thus highlighting their essential role in microbial decay. Further, we reveal that many of these microbial proteins from Pseudomonas are ribosomal proteins, promoting enzyme synthesis by enhancing transcription and translation. This study provides intrinsic insights into the underlying mechanisms by which microorganisms contribute to meat spoilage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Liver cancer is the third leading cause of cancer-related mortality worldwide. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer is driven by complex genetic, epigenetic, and environmental factors. MicroRNAs, a class of naturally-occurring small non-coding RNAs play crucial roles in HCC by simultaneously modulating expression of multiple genes in a fine-tuning manner. Significant progress has been made in understanding how miRNAs influence key oncogenic pathways, including cell proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT), as well as their role in modulating the immune microenvironment in HCC. Due to the unexpected stability of miRNAs in the blood and fixed HCC tumors, recent advancements also highlight their potential as non-invasive diagnostic tools. Restoring or inhibiting specific miRNAs have offered promising strategies for targeted HCC treatment by suppressing malignant hepatocyte growth and enhancing antitumor immunity. In this comprehensive review, we consolidate previous research and provide the latest insights into how miRNAs regulate HCC and their therapeutic and diagnostic potential. We delve into dysregulation of miRNA biogenesis in HCC, the roles of miRNAs in proliferation and apoptosis of malignant hepatocytes, angiogenesis and metastasis of HCC, immune microenvironment in HCC and drug resistance. We also discuss the therapeutic and diagnostic potential of miRNAs and delivery approaches of miRNA drugs to overcome the limitations of current HCC treatment options. By thoroughly summarizing the roles of miRNAs in HCC, our goal is to advance the development of effective therapeutic drugs with minimal adverse effects and to establish precise tools for early diagnosis of HCC., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Eosinophilic esophagitis (EoE) and celiac disease are both chronic T helper cell-mediated inflammatory conditions of the digestive tract. Although an association between these two conditions has been suggested, it has not been well characterized in a real-world setting., Goals: Our objective was to better examine the association between celiac disease and EoE using a real-world population database., Study: This was a retrospective cohort study of data using TriNetX, a global population database, to identify patient records using International Classification of Disease 10 (ICD-10) codes. We organized participants into six distinct cohorts predicated on age and diagnoses of celiac disease and EoE between April 28, 2003, and April 28, 2023. Patient demographics, prevalence, incidence, and medical characteristics of each cohort were extracted., Results: Among 46,398 patients with EoE and 84,383 patients with celiac disease, individuals with EoE demonstrated a higher prevalence (2.76%) and incidence (329/100,000 persons/year) of celiac disease compared with those without EoE (0.21% prevalence and 146/100,000 incidence, between 2021 and 2023). A concurrent diagnosis of both conditions increased the risk of asthma (RR: 2.00 pediatric, 1.82 adult), allergic rhinitis (RR: 2.35 pediatric, 1.81 adult), atopic dermatitis (RR: 3.28 pediatric, 2.07 adult), and rheumatoid arthritis (RR: 3.53 pediatric, 1.41 adult). In addition, patients with celiac disease with EoE exhibited a heightened risk for iron deficiency anemia (aHR 1.789; 95% CI: 1.166 to 2.745)., Conclusions: Both the incidence and prevalence of EoE are elevated in patients with celiac disease and vice versa. These concurrent diagnoses affect disease characteristics and heighten the risk of complications in celiac disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Despite the fact that endometriosis is a common gynecological disease that occurs in 10% of women of reproductive age, the pathogenesis and treatment strategy are not clear to date. Endometriosis patients commonly characterized by adhesions in the pelvis or ovaries, which leads to prolonged inflammation in the abdominal cavity. To handle the chronic inflammation, changes of immune cells including T-cell, NK cells and macrophage are accompanied. Therefore, diverse cytokines and adhesions of abdominal cavity lead poor quality of ovarian follicles, inappropriate response to the hormone and infertility. This review will guide researchers to summarize the molecular changes and identify new treatment strategies for endometriosis mediated inflammation and pregnancy failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In magnetic resonance imaging (MRI), quantitative measurements of analytes are hindered by difficulties in distinguishing the MRI signals of activation of the probe by the analyte from those of the accumulation of the intact probe. Here we show that imaging sensitivity and quantitation can be enhanced by ratiometric MRI probes with a high relaxivity-ratio change (more than 2.5-fold at 7 T) via magnetic-susceptibility-dependent magnetic resonance tuning. Specifically, polymeric probes that incorporate paramagnetic Mn-porphyrin and superparamagnetic iron oxide nanoparticles inducing opposite changes in the longitudinal and transverse magnetic relaxivities responded to analyte concentration independently of probe concentration. In mice, the probes allowed for quantitative real-time dynamic imaging of H 2 O 2 , H 2 S or pH in subcutaneous tumours, in livers with drug-induced injury and in orthotropic gliomas. The ratiometric MRI probes may be advantageously used to obtain molecular insight into pathological processes and to circumvent interference from dynamic changes in probe concentration within the body while providing anatomical information., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Brain takes up approximately 20% of the total body oxygen and glucose consumption due to its relatively high energy demand. Glucose is one of the major sources to generate ATP, the process of which can be realized via glycolysis, oxidative phosphorylation, pentose phosphate pathways and others. Lactate serves as a hub molecule amid these metabolic pathways, as it may function as product of glycolysis, substrate of a variety of enzymes and signal molecule. Thus, the roles of lactate in central nervous system (CNS) diseases need to be comprehensively elucidated. Histone lactylation is a novel lactate-dependent epigenetic modification that plays an important role in immune regulation and maintaining homeostasis. However, there's still a lack of studies unveiling the functions of histone lactylation in the CNS. In this review, we first comprehensively reviewed the roles lactate plays in the CNS under both physiological and pathological conditions. Subsequently, we've further discussed the functions of histone lactylation in various neurological diseases. Furthermore, future perspectives regarding histone lactylation and its therapeutic potentials in stroke are also elucidated, which may possess potential clinical applications., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The unique microenvironment within living cells, characterized by high glutathione levels, reactive oxygen species concentrations, and active enzymes, facilitates the execution of chemical reactions. Recent advances in organic chemistry and chemical biology have leveraged living cells as reactors for chemical synthesis. This review summarizes recent reports on key intracellular in situ synthesis processes, including the synthesis of near-infrared fluorescent dyes, intracellular oxidative cross-linking, bioorthogonal reactions, and intracellular polymerization reactions. These methods have been applied to fluorescence imaging, tumor treatment, and the enhancement of biological functions. Finally, we discuss the challenges and opportunities in the field of in situ intracellular synthesis. We aim to guide the design of chemical molecules for in situ synthesis, improving the efficiency and control of artificial reactions in living cells, and ultimately achieving cell factory-like exogenous biological synthesis, biological function enhancement, and biomedical applications.

To endow non-antibacterial molecules with highly efficient bactericide activity is an important but challenging issue. Herein, a kind of cell-penetrating peptide octa-arginine (R8) is found to be effective in activating antibacterial ability when assembling with anionic surfactant sodium dodecyl sulfate (SDS), while individual R8 or SDS shows poor or no antibacterial ability. By combined electrostatic, hydrogen bond, and hydrophobic interactions, R8 and SDS associate into wormlike micelle and lamellar structure by forming supramolecular self-assembling units, depending on their charge ratio (CR). The lamellar aggregates show particularly high antibacterial activities against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Interestingly, E. coli and S. aureus are killed by membrane-disrupting and membrane-penetrating mechanisms, respectively. Furthermore, in vivo experiments evidence that the R8/SDS lamellar aggregates accelerate the recovery of bacteria-infected wounds, wherein the reduced inflammation and promoted angiogenesis are clearly presented. This study proves that highly efficient bactericidal activity is triggered by the synergistic action of penetrating peptide and anionic amphiphiles, thus providing a new strategy to realize highly efficient and targetable antibacterial application., (© 2024 Wiley‐VCH GmbH.)

Thiol flavor compounds are a class of flavoring ingredients that contribute significantly to food flavor. However, rapid discrimination of multiple thiol-flavor compounds remain a challenge. In this study, a ratiometric fluorescent sensor (TPE-ssHPA@Cu NCs-Ce 3+ ) with dual-channel fluorescence features was developed using tetraphenylethene-embedded hyperbranched poly(amidoamine) as a template to stabilize the copper nanocluster‑cerium ions. The sensor was explored for the specific discrimination of six typical thiol flavor compounds, each producing diverse fluorescent fingerprints that were further identified using pattern recognition methods. The sensor achieved a rapid response in identifying thiol flavor compounds and multicomponent mixtures, with detection limits of 0.32-3.13 μM. Furthermore, it was successfully applied to differentiate between the different types and cooking times of meat broths., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A series of pyridinium-indolocarbazole oligomers with different lengths, capable of adopting helical conformations with tubular cavities, has been synthesized. These oligomers can accommodate two, three, or four iodide ions in a linear arrangement within their cavities, which can be exchanged with other halides.

Nitric oxide (NO), a pivotal signalling molecule, plays multifaceted roles in physiological and pathological processes, including cardiovascular and immune functions, neurotransmission and cancer progression. Nevertheless, measuring NO in vivo is challenging due to its transient nature and the complexity of the biological environment. Here we describe NO-responsive magnetic probes made of crosslinked superparamagnetic iron oxide nanoparticles tethered to a NO-sensitive cleavable linker for highly sensitive and selective NO magnetic resonance imaging in vivo. These probes enable the detection of NO at concentrations as low as 0.147 μM, allowing for the imaging and quantification of NO in mouse tumour models, studying its effects on tumour progression and immunity and assessing the response of tumour-associated macrophages to cancer immunotherapeutic agents. Additionally, they facilitate concurrent anatomical and molecular imaging of organs, helping to identify pathological alterations in the liver. Overall, these probes represent promising non-invasive tools for investigating the dose-dependent conflicting role of NO in physiological and pathophysiological processes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A novel near-zero-discharge recirculating aquaculture system was successfully set up and ran for six months or above. A uniquely designed and 3D printed poly (lactic acid) (PLA) structure was applied as carbon source. The system achieved over 50 % daily nitrogen removal capability and maintained a low NO 3 -N level of <0.5 mg/L. Steady water quality was observed throughout the experiment period. Microbial distribution was studied and top abundant microorganisms and their general functions in carbon and nitrogen utilization were discussed. Denitrification and L-glutamate formation were identified as two main nitrogen pathways. The cooccurrence network connecting various genera and multiple functions was revealed. Subtilisin was one important PLA degrading enzymes in the system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Studies focusing on the kinematics of the ankle joint complex (AJC) have long been a key area of interest for biomechanists and orthopedic surgeons. However, it is not clear how additional weight-bearing walking affects the motion of the AJC compared to walking with a normal body weight (BW) or what adjustments the AJC would instinctively make to accommodate the additional load. To address this gap in knowledge, advanced dynamic biplane radiography combined with a model-based 2D-3D tracking technique was employed to elucidate the inherent kinematics of the AJC during the stance phase while walking with and without additional weight-bearing. It was found that walking with additional 50% body weight (BW + 50%) resulted in a greater dispersion of instantaneous axes of rotation in the talocrural and subtalar joints during the stance phase of gait. The talocrural joint is more plantarflexed and anteriorly translated during the early and late stance phases than during the midstance phases, which suggests that additional weight-bearing affects the stability of the AJC. Moreover, walking with BW + 50% showed that the center of rotation of the talocrural joint was positioned more superiorly and posteriorly during the foot flat to heel-off phase. This, accordingly, increases the ankle-foot gear ratio and the force of the dorsiflexors., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

ClinVar (www.ncbi.nlm.nih.gov/clinvar/) is a free, public database of human genetic variants and their relationships to disease, with >3 million variants submitted by >2800 organizations across the world. The database was recently updated to have three types of classifications: germline, oncogenicity and clinical impact for somatic variants. As for germline variants, classifications for somatic variants can be submitted in batches in a file submission or through the submission API; variants can also be submitted and updated one at a time in online submission forms. The ClinVar XML files were redesigned to allow multiple classification types. Both old and new formats of the XML are supported through the end of 2024. Data for somatic classifications were also added to the ClinVar VCF files and to several tab-delimited files. The ClinVar VCV pages were updated to display the three types of classifications, both as it was submitted and as it was aggregated by ClinVar. Clinical testing laboratories and others in the cancer community are invited to share their classifications of somatic variant classifications through ClinVar to provide transparency in genomic testing and improve patient care., (Published by Oxford University Press on behalf of Nucleic Acids Research 2024.)

A highly aggressive neoplastic disease, pancreatic ductal adenocarcinoma (PDAC) is documented as the third chief cause of cancer-associated mortality in both sexes combined in the United States. For decades, gemcitabine-based chemotherapy has been embraced as a cornerstone drug for the treatment of PDAC. However, there have been several unsolved problems, including cytotoxicity, and chemoresistance. Gemcitabine efficacy was attributed to the attenuation of ribonucleotide reductase subunit-M1 (RRM1). Overexpression of RRM1 in PDAC is highly correlated with gemcitabine resistance and reduced gemcitabine sensitivity, resulting in a poor survival rate even after gemcitabine treatment. Moreover, the status of TP53, a tumor suppressor gene, assumes a decisive role in the response of PDAC to gemcitabine. Therefore, targeting RRM1 and P53 might be a therapeutic strategy for strengthening gemcitabine efficacy and cytotoxicity against PDAC. Alpinumisoflavone (AIF) is a prenylated isoflavone originated in Cudrania tricuspidate with versatile bioactive properties, including anticancer activity. However, there was no report whether AIF can exert anticancer effect and exhibit synergistic effect with gemcitabine against PDAC. Therefore, the anticancer properties of AIF were assessed with PANC-1 and MIA PaCa-2. In addition, synergism between AIF and gemcitabine were analyzed. Moreover, the contribution of P53 and RRM1 expression to gemcitabine resistance was assessed by comparing their protein levels in PDAC cells and normal pancreatic cells. The interactions of AIF with RRM1 protein were confirmed by molecular docking and dynamics simulation. Therefore, AIF enhances gemcitabine efficacy against PDAC through the regulation of P53 and RRM1., Competing Interests: Declaration of competing interest None of the contributing authors have any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Immunotherapy has become the primary option for recurrent and metastatic nasopharyngeal cancer (R/M NPC) after failure of chemotherapy, but without good prognostic indicators. Our study aimed to assess the potential of the systemic immune-inflammation index (SII) in predicting the effectiveness of PD-L1 inhibitor therapy for R/M NPC., Patients and Methods: The study cohort comprises of a prospective Phase 2 clinical trial population undergoing PD-L1 inhibitor for R/M NPC at 42 hospitals in China between 2019 and 2021. The SII is classified into high and low states based on the optimal threshold determined by the ROC curve. We assessed the relationship between SII status and objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) using regression analyses and Kaplan-Meier method. We performed sensitivity analyses to confirm the results., Results: Our study analyzed 153 patients from one of the largest cohorts to date of R/M NPC treated with PD-L1 inhibitor and found that SII showed a significant association with prognosis. We found higher ORR and DCR in the SII-Low group. Univariate analyses demonstrated that SII independently predicted DCR (OR, 0.43; 95% CI, 0.22-0.84; p = 0.001), PFS (HR, 1.85; 95% CI, 1.31-2.62; p < 0.001) and OS (HR, 1.92; 95% CI, 1.29-2.85; p < 0.001). After adjusting for covariates, multivariate analysis remains relevant. [DCR (OR, 0.47; 95% CI, 0.22-0.99; p = 0.048), PFS (HR, 1.72; 95% CI, 1.2-2.47; p =0.003); OS (HR, 2.08; 95% CI, 1.38-3.13; p < 0.001)]. Sensitivity analyses also support this conclusion., Conclusion: SII may well provide predictive value for the efficacy and prognosis of patients with R/M NPC treated with PD-L1 inhibitor. Patients with high status of SII may have a poorer therapeutic effect and survival., Competing Interests: Junyou Ge, Yan Qing and Youneng Wei are employees of Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd (Chengdu, China). All other authors declare no potential conflicts of interest., (© 2024 Song et al.)

Protein activity, abundance, and stability can be regulated by posttranslational modification including ubiquitination. Ubiquitination is conserved among eukaryotes and plays a central role in modulating cellular function, yet we lack comprehensive catalogs of proteins that are modified by ubiquitin in plants. In this study, we describe an antibody-based approach to enrich ubiquitinated peptides coupled with isobaric labeling to enable quantification of up to 18-multiplexed samples. This approach identified 17,940 ubiquitinated lysine sites arising from 6,453 proteins from Arabidopsis (Arabidopsis thaliana) primary roots, seedlings, and rosette leaves. Gene ontology analysis indicated that ubiquitinated proteins are associated with numerous biological processes including hormone signaling, plant defense, protein homeostasis, and metabolism. We determined ubiquitinated lysine residues that directly regulate the stability of three transcription factors, CRYPTOCHROME-INTERACTING BASIC-HELIX-LOOP-HELIX 1 (CIB1), CIB1 LIKE PROTEIN 2 (CIL2), and SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) using in vivo degradation assays. Furthermore, codon mutation of CIB1 to create a K166R conversion to prevent ubiquitination, via CRISPR/Cas9-derived adenosine base editing, led to an early flowering phenotype and increased expression of FLOWERING LOCUS T (FT). These comprehensive site-level ubiquitinome profiles provide a wealth of data for future functional studies related to modulation of biological processes mediated by this posttranslational modification in plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: Ventriculoperitoneal (VP) shunt surgery is the primary treatment for patients with idiopathic normal pressure hydrocephalus (iNPH). This study compares the outcomes of VP shunt placement using electromagnetic (EM) navigation versus standard methods in iNPH patients, focusing on catheter accuracy and post-operative complication rates., Methods: This retrospective study included 31 iNPH patients who underwent standard shunts using anatomical landmarks and 50 iNPH patients who underwent EM-guided shunts. Parameters assessed included shunt placement grade, catheter tip position, catheter angle, puncture attempts, operative duration, postoperative infection rates, intraparenchymal hemorrhage rates, and shunt malfunction rates. Patients were followed up at 3, 6, 12, and 24 months after surgery or until shunt failure., Results: In the EM-guided group, a higher percentage of Grade 1 shunt placements (92% vs. 71%, p = 0.03) and fewer Grade 3 placements (2% vs. 13%, p = 0.068) were observed. The catheter tip position at the foramen of Monro was significantly more accurate (p < 0.001), with smaller lateral catheter deviation angles in both coronal (19.69° vs. 24.2°, p < 0.0001) and sagittal sections (21.75° vs. 39.3°, p < 0.01). The EM-guided group had fewer puncture attempts, shorter operative durations, lower incidence of intraparenchymal hemorrhage (p < 0.01), and fewer shunt malfunctions over the 2-year follow-up period (2% vs. 26%, p = 0.0003)., Conclusions: The use of EM navigation in VP shunts for iNPH patients improves catheter placement accuracy, reduces postoperative complications and shunt malfunction rates, and provides precise and individualized surgical treatment., (Copyright © 2024. Published by Elsevier Inc.)

Chromochloris zofingiensis has been proven as a potential resource for large-scale astaxanthin production, but little information on phytohormones for its growth and astaxanthin accumulation could be obtained. This study explored the impact of gibberellic acid-3 (GA3) on growth and astaxanthin biosynthesis in heterotrophic C. zofingiensis . After 6 days of cultivation with GA3, biomass and astaxanthin yields in 7.5 L fermenters reached 268.5 g·L -1 and 0.34 g·L -1 , respectively, which were 6% and 89% higher than those in the control. GA3 changed transcription levels of genes linked to carbon metabolism, lipid metabolism, astaxanthin production, and ABC transporters. Genes related to astaxanthin biosynthesis, such as phytoene synthase ( PSY ), phytoene desaturase ( PDS ), beta-carotenoid hydroxylase ( CHYb ), and beta-carotenoid ketolase ( BKT ), were up-regulated under GA3 induction. The enhancement of carbon metabolism and lipid metabolism led to elevated consumption of substrates and generation of reducing power, thus facilitating astaxanthin biosynthesis. By using GA3 and arginine together, the astaxanthin yield increased to 0.39 g·L -1 , which was 18% higher than that obtained under GA3 induction. It could be concluded that GA3 showed significant effects on astaxanthin biosynthesis. This research proposed novel feasible approaches to enhance astaxanthin production in heterotrophic C. zofingiensis .